7PDC

The structure of the human tetrameric LL-37 peptide in a channel conformation

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7PDC の概要

• エントリーDOI: 10.2210/pdb7pdc/pdb
• 分子名称: Cathelicidin antimicrobial peptide, CHLORIDE ION (3 entities in total)
• 機能のキーワード: antimicrobial peptide, ll-37, channel, antimicrobial protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9044.15

構造登録者

Zeth, K.,Sancho-Vaello, E. (登録日: 2021-08-05, 公開日: 2021-09-08, 最終更新日: 2024-01-31)

主引用文献

Sancho-Vaello, E.,Gil-Carton, D.,Francois, P.,Bonetti, E.J.,Kreir, M.,Pothula, K.R.,Kleinekathofer, U.,Zeth, K.
The structure of the antimicrobial human cathelicidin LL-37 shows oligomerization and channel formation in the presence of membrane mimics.
Sci Rep, 10:17356-17356, 2020

PubMed Abstract: The human cathelicidin LL-37 serves a critical role in the innate immune system defending bacterial infections. LL-37 can interact with molecules of the cell wall and perforate cytoplasmic membranes resulting in bacterial cell death. To test the interactions of LL-37 and bacterial cell wall components we crystallized LL-37 in the presence of detergents and obtained the structure of a narrow tetrameric channel with a strongly charged core. The formation of a tetramer was further studied by cross-linking in the presence of detergents and lipids. Using planar lipid membranes a small but defined conductivity of this channel could be demonstrated. Molecular dynamic simulations underline the stability of this channel in membranes and demonstrate pathways for the passage of water molecules. Time lapse studies of E. coli cells treated with LL-37 show membrane discontinuities in the outer membrane followed by cell wall damage and cell death. Collectively, our results open a venue to the understanding of a novel AMP killing mechanism and allows the rational design of LL-37 derivatives with enhanced bactericidal activity.

PubMed: 33060695
DOI: 10.1038/s41598-020-74401-5

実験手法

X-RAY DIFFRACTION (1.83 Å)